The occurrence of a short-lived suppressor cell will be investigated in normal individuals, patients with systemic lupus erythematosus and other diseases and in NZB-NZW F1 hybrid mice. The development of a suppressor cell during cultures of human lymphocytes will also be investigated in similar groups of subjects. Mechanisms involved in B lymphocyte differentiation will be studied and alterations in these mechanisms in patients with hypergammaglobulinemia and autoimmune disease examined. The effects of combined injections of thymosin and thymocytes on the established autoimmune disease of New Zealand mice will be investigated. The influence of exposure of normal mice to New Zealand mice will also be investigated. In vitro techniques will be utilized to study immunologic abnormalities in NZB/NZW F1 hybrid mice. These will include induction of tolerance and B cell activation. The mechanism of the deposition of DNA-anti-DNA complexes in the subepidermal region of the skin will be studied in systemic lupus erythematosus. Radioimmunoassay methods will be developed for the measurement of anti-Sm antibody and anti-ribonucleoprotein antibody in patients with mixed connective tissue disease. The presence in rheumatoid cartilage of antigens capable of stimulating the lymphocytes of the rheumatoid synovial membrane will be investigated. The mechanism of action of gold salts and penicillamine on rheumatoid inflammation will be studied.